Age-related macular degenerations (AMD) is a highly prevalent retinal disease in the elderly. The most prominent histopathological and clinical signs of AMD are subcellular lesions (drusen and basal linear deposits), which are neutral lipid-rich subcellular lesions that develop behind the retinal pigment epithelium. Drusen and BLinD are two physical forms—lump and layer—of the same lipid-rich lipoprotein derived debris. Progress towards understanding pathogenic mechanisms involved in macular degeneration and testing new treatments has been hindered by the lack of an accurate model system such as an engineered mouse that exhibits the pathognomonic lesions of the disease, (e.g., drusen and basal linear deposits (BlinD).
The RPE is simple cuboidal epithelium specialized to maintain the health of photoreceptors and the choroidal vasculature while maintaining the outer limits of the physiological blood-retina barrier. Research shows that RPE cells are phenotypically unstable when removed from their host eye and maintained under routine tissue culture conditions. Under these conditions, RPE can undergo a progression of phenotype changes resulting in cells that resemble myofibroblasts rather than epithelia. (Guidry et al. Invest. Ophthalmol. Vis. Sci. 43(1):267-273 (2002)). For this reason, the overwhelming majority of research published in the scientific literature involves immortalized cell lines, fetal cells or primary cells that have trans-differentiated into the myofibroblast phenotype.
The present invention overcomes previous shortcomings in the art by providing a RPE primary cell system that produces subcellular deposits as model for the study of macular degeneration.